medwireNews: Phase 3 results from China suggest that paclitaxel plus carboplatin could be an adjuvant therapy option for patients with operable triple-negative breast cancer (TNBC).
The combination was associated with significantly better disease-free survival (DFS) and relapse-free survival (RFS) than the standard anthracycline–taxane regimen, report Ke-Da Yu (Fudan University, Shanghai) and fellow PATTERN researchers in JAMA Oncology.
“However, the results should be considered with caution, as high-level evidence is still lacking to make platinum-based chemotherapy the new standard of care,” they add.
After a median follow-up of 62 months, the 5-year DFS rate was 86.5% for the 325 Chinese women with pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter greater than 10 mm who were randomly allocated to receive adjuvant paclitaxel 80 mg/m2 plus carboplatin AUC2 on days 1, 8, and 15 every 28 days for six cycles.
This was significantly higher than the 80.3% rate for their 322 counterparts who instead received three cycles of cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, and fluorouracil 500 mg/m2 every 3 weeks followed by three cycles of 3-weekly docetaxel 100 mg/m2, and equated to a hazard ratio (HR) of 0.65 favoring the platinum-based regimen.
The 5-year RFS rate was similarly significantly improved with paclitaxel plus carboplatin relative to the control regimen, at 91.2% versus 84.4% (HR=0.54), and there was a trend towards improved 5-year distant DFS with the platinum-based chemotherapy, at 92.6% and 87.9%, respectively (HR=0.59).
However, overall survival (OS) did not differ significantly between the paclitaxel–carboplatin and control study arms, with a respective 93.4% and 89.8% alive at the 5-year mark, and “adequate efficacy assessment of [paclitaxel–carboplatin] on OS will require long-term follow-up and more events,” say Yu and colleagues.
Exploratory subgroup analysis of DFS indicated that women aged younger than 50 years and those with grade III disease derived greater benefit from the platinum-based regimen than older women and those with grade I–II tumors, respectively.
Although platinum agents are considered to be “particularly active in cancer cells with DNA repair deficiency,” the researchers did not find a significant difference in the DFS benefit afforded by the paclitaxel–carboplatin combination between women with versus without germline BRCA1/2 mutations.
But further analysis of 12 genes involved in homologous recombination repair (including BRCA1/2) showed a significant treatment benefit of the platinum regimen in participants harboring deleterious variants in these genes, with a 5-year DFS rate of 88.4% versus 76.3% with the control (HR=0.39). No such association was observed among noncarriers.
Yu et al caution, however, that these findings are “hypothesis-generating, and further prospective randomized trials are required to confirm our results.”
And they conclude that research into “identifying predictive biomarkers is imperative for the selection of appropriate patients for platinum-based regimens in the adjuvant setting.”
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